title: Inhibition of accelerated rejection mediated by alloreactive CD4⁺ memory T cells and prolonged allograft survival by arsenic trioxide.
abstract: The aim of this study was to evaluate and determine the potential mechanisms of As₂O₃ in accelerated rejection mediated by alloreactive CD4⁺ memory T cells. Vascularized heterotopic cardiac transplantation from C57BL/6 mice to nude mice (pre-transferred CD4⁺ memory T cells) was performed on Day 0, and As₂O₃ was administered to recipient mice from Day 0 to 10. As a result, As₂O₃ could reduce the proliferation of allo-primed CD4⁺ memory T cells in vitro in MLR and the baseline rate of proliferation was restored by the addition of exogenous IL-2. In vivo, compared with the control[+] group, the mean survival time of cardiac allografts in the As₂O₃ group was prolonged from 5.8 ± 0.7 to 14.2 ± 2.5 days. Five days after transplantation, the relative gene expression of IL-2, IFN-γ and Foxp3 was reduced in the grafts by As₂O₃ treatment, but the expression of IL-10 and TGF-β was increased. Correspondingly, the proportions of CD4⁺ T cells, CD4⁺ memory T cells and regulatory T cells (Tregs), both in recipient spleens and lymph nodes, were lowered. These results indicate the potential of As2O3 as a novel immunosuppressant targeting CD4⁺ memory T cells.
authors.affiliation: Basic Medical Department of Medical College, Xiamen University, Xiamen City, Fujian Province, P. R. China.
authors.forename: Guoliang
authors.initials: G
authors.lastname: Yan
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xi
authors.forename: Shuangyue
authors.initials: S
authors.lastname: Xu
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
authors.forename: Jibing
authors.initials: J
authors.lastname: Chen
authors.forename: Helong
authors.initials: H
authors.lastname: Dai
authors.forename: Junjie
authors.initials: J
authors.lastname: Xia
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Zhi
authors.initials: Z
authors.lastname: Li
authors.forename: Zhongquan
authors.initials: Z
authors.lastname: Qi
mesh_terms: D019264:Adoptive Transfer; D064591:Allografts / Q000276:immunology; D000818:Animals; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage*; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006084:Graft Rejection / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D016027:Heart Transplantation; D007156:Immunologic Memory; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010087:Oxides / Q000008:administration & dosage*; D011183:Postoperative Complications / Q000276:immunology* / Q000517:prevention & control; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology / Q000637:transplantation
chemical_list: D001152:Arsenicals; D007166:Immunosuppressive Agents; D010087:Oxides; D000077237:Arsenic Trioxide